Pharmacological Approaches to Drug Repurposing: Mechanisms, Strategies, and Clinical Applications

Drug repurposing has emerged as a strategic approach to accelerate therapy development by identifying novel uses for existing drugs, offering reduced development time, lower costs, and established safety profiles. This review provides a comprehensive analysis of pharmacological approaches to drug repurposing, focusing on mechanisms, strategic paradigms, and clinical applications. A structured literature search was conducted across PubMed, Scopus, Web of Science, and Google Scholar using keywords such as “drug repurposing,” “mechanism-based repurposing,” and “phenotype-driven repurposing,” considering articles published in English from 2015 to 2026. Studies reporting mechanistic insights, computational strategies, preclinical and clinical evidence, and regulatory considerations were included, while non-peer-reviewed or insufficiently detailed studies were excluded. Data were extracted on drug names, original and repurposed indications, mechanisms, strategies employed, and clinical outcomes. The review identified multiple successful repurposing examples, including sildenafil, thalidomide, metformin, and remdesivir, highlighting the role of both phenotype-driven and mechanism-based approaches. Computational methods, such as in silico predictions, network pharmacology, and machine learning, were found to significantly enhance identification of novel indications. Despite regulatory, intellectual property, and safety challenges, repurposed drugs demonstrated meaningful clinical impact across oncology, infectious diseases, and neurodegenerative disorders. These findings underscore drug repurposing as an evidence-driven, translational strategy that expands therapeutic options, informs clinical practice, and guides future pharmacological research.